Nitric oxide cytoskeletal-induced alterations reverse the endothelial progenitor cell migratory defect associated with diabetes
Nitric oxide cytoskeletal-induced alterations reverse the endothelial progenitor cell migratory defect associated with diabetes
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DOI：
10.2337/diabetes.55.01.06.db05-0803
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发表时间：
2006-01-01
期刊：
影响因子：
7.7
通讯作者：
Grant, MB
中科院分区：
文献类型：
--
作者：
Segal, MS;Shah, R;Grant, MB
基质衍生因子-1（SDF-1）是内皮祖细胞（EPC）募集到缺血区域的关键趋化因子，使这些细胞参与代偿性血管生成。SDF-1受体CXCR 4在发育中的血管以及CD 34 + EPCs上表达。我们描述了皮摩尔和纳摩尔浓度的SDF-1对新血管形成的影响不同，诱导CD 34+细胞迁移和EPC管形成。从糖尿病患者分离的CD 34+细胞表现出向SDF-1迁移的明显缺陷。在一些但不是所有患者中，这种缺陷与CD 26/二肽基肽酶IV（一种使SDF-1失活的酶）的细胞表面活性相关。糖尿病CD 34+细胞也不响应血管内皮生长因子而迁移，并且结构刚性。然而，将CD 34+细胞与一氧化氮（NO）供体一起孵育可纠正这种迁移缺陷并纠正细胞变形性。此外，外源性NO改变血管扩张剂刺激的磷蛋白和EPCs中的钙激活分布。这些数据支持糖尿病CD 34+细胞中常见的下游细胞骨架改变，其独立于生长因子受体活化，并且可以用外源性NO校正。糖尿病EPCs对SDF-1的反应能力的丧失可能导致糖尿病患者异常的组织血管形成和内皮修复。
Stromal-derived factor-1 (SDF-1) is a critical chemokine for endothelial progenitor cell (EPC) recruitment to areas of ischemia, allowing these cells to participate in compensatory anglogenesis. The SDF-1 receptor, CXCR4, is expressed in developing blood vessels as well as on CD34+ EPCs. We describe that picomolar and nanomolar concentrations of SDF-1 differentially influence neovascularization, inducing CD34+ cell migration and EPC tube formation. CD34+ cells isolated from diabetic patients demonstrate a marked defect in migration to SDF-1. This defect is associated, in some but not all patients, with a cell surface activity of CD26/dipeptidyl peptidase IV, an enzyme that inactivates SDF-1. Diabetic CD34+ cells also do not migrate in response to vascular endothelial growth factor and are structurally rigid. However, incubating CD34+ cells with a nitric oxide (NO) donor corrects this migration defect and corrects the cell deformability. In addition, exogenous NO alters vasodilator-stimulated phosphoprotein and mammalian-enabled distribution in EPCs. These data support a common downstream cytoskeletal alteration in diabetic CD34+ cells that is independent of growth factor receptor activation and is correctable with exogenous NO. This inability of diabetic EPCs to respond to SDF-1 may contribute to aberrant tissue vascularization and endothelial repair in diabetic patients.